Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

33234057

DOI Digital object identifier for electronic documents.

https://doi.org/10.1089/thy.2020.0193

URI Uniform resource identifier for web resources.

Authors

Jiang W, Yu X, Kosik RO, Song Y, Qiao T, Tong J, Liu S, Fan S, Luo Q, Chai L, Lv Z, Li D

Journal

Thyroid : official journal of the American Thyroid Association

Year

2021

Keywords:

16S rRNA sequencing, Graves' disease, alpha diversity, gut microbiota, metabolism

Background: Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. Methods: The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Results: Compared with controls, GD patients had reduced alpha diversity (p < 0.05). At the phylum level, GD patients had a significantly lower proportion of Firmicutes (p = 0.008) and a significantly higher proportion of Bacteroidetes (p = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of Bacteroides and Lactobacillus, although fewer Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group than controls (all p < 0.05). Subgroup analysis of GD patients revealed that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that Blautia may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all p < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Conclusions: Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.

Experiment 1

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Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Graves disease Basedow disease,Basedow's disease,exophthalmic goiter,Flajani-Basedow-Graves disease,grave's disease,Graves disease,Graves' disease,Graves' hyperthyroidism,parry disease,toxic diffuse goiter,graves disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy controls (HC)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Graves’ disease (GD)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Graves’ disease (GD) patients (12 males, 33 females, ages 16–65 years, median age 37) recruited from the Department of Nuclear Medicine at the Shanghai Tenth People's Hospital from January to June 2019.

Group 0 sample size Number of subjects in the control (unexposed) group: 59

Group 1 sample size Number of subjects in the case (exposed) group: 45

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): One month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Richness Number of species: decreased

Signature 1

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Curated date: 2025/07/24

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 3C and 3D

Description: The LEfSe was used to identify the species that significantly differed between GD patients and HC at the phylum and genus levels. Only taxa meeting a significant LDA threshold value of >3 and p < 0.05 are shown.

Abundance in Group 1: increased abundance in Graves’ disease (GD)

NCBI	Quality Control	Links
Bacteroidota
Bacteroides
Lactobacillus

Revision editor(s): Aleru Divine

Signature 2

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Source: Figure 3C and 3D

Description: The LEfSe was used to identify the species that significantly differed between GD patients and HC at the phylum and genus levels. Only taxa meeting a significant LDA threshold value of >3 and p < 0.05 are shown.

Abundance in Group 1: decreased abundance in Graves’ disease (GD)

NCBI	Quality Control	Links
Bacillota
Blautia
Anaerobutyricum hallii
Anaerostipes
Dorea
unclassified Peptostreptococcaceae
Collinsella
[Ruminococcus] torques
Oscillospiraceae UCG 002Oscillospiraceae UCG 002
Oscillospiraceae UCG 013Oscillospiraceae UCG 013
Clostridium
Butyricicoccus
Eubacterium ventriosum
Christensenellaceae R7 groupChristensenellaceae R7 group
Coprococcus
Ruminococcus gauvreauii
Muribaculaceae

Revision editor(s): Aleru Divine

Experiment 2

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Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Graves disease , Hashimoto's thyroiditis Basedow disease,Basedow's disease,exophthalmic goiter,Flajani-Basedow-Graves disease,grave's disease,Graves disease,Graves' disease,Graves' hyperthyroidism,parry disease,toxic diffuse goiter,graves disease,autoimmune thyroiditis,chronic lymphocytic thyroiditides,chronic lymphocytic thyroiditis,disease, Hashimoto,disease, Hashimoto's,Hashimoto disease,Hashimoto struma,Hashimoto syndrome,Hashimoto thyroiditides,Hashimoto Thyroiditis,Hashimoto thyroiditis,Hashimoto's disease,Hashimoto's struma,Hashimoto's syndrome,Hashimoto's syndromes,Hashimoto's thyroiditis,Hashimotos disease,Hashimotos syndrome,HT,Ht,hypothyroidism, autoimmune,hypothyroidism, autoimmune thyroid autoantibodies, included,Lymphocytic Thyroiditides,lymphocytic thyroiditides, chronic,Lymphocytic Thyroiditis,lymphocytic thyroiditis,lymphocytic thyroiditis, chronic,Lymphomatous Thyroiditides,syndrome, Hashimoto's,syndromes, Hashimoto's,thyroid autoantibodies,thyroiditides, chronic lymphocytic,thyroiditides, Hashimoto,Thyroiditides, Lymphocytic,Thyroiditides, Lymphomatous,thyroiditis, chronic lymphocytic,thyroiditis, Hashimoto,Thyroiditis, Lymphocytic,Thyroiditis, Lymphomatous,hashimoto's thyroiditis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Hashimoto's negative

Group 1 name Corresponds to the case (exposed) group for case-control studies: Hashimoto's positive

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Graves’ disease (GD) patients with Hashimoto's thyroiditis